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PubMed1981

Effects of diazepam on operant behavior in man.

The effects of diazepam (10 mg orally) on the responding of normal human volunteers was studied in a procedure that involved the maintenance of operant behavior by monetary reinforcement and its suppression by monetary loss (punishment). Diazepam produced an antipunishment effect as shown by an increase in behavior suppressed by monetary loss. An analogy to animal procedures that selectively detect antianxiety drugs is apparent.

Adult↗
PubMed1979

Mutual antagonism of behavioral effects of TRH and thiobarbiturate on an operant task in rhesus monkeys.

Similar excitatory or depressant response rate dependent effects on monkeys responding on a variable interval reinforcement schedule were observed following intravenous administration of either thyrotropin releasing hormone (TRH) or thiobarbiturate. However, these agents were mutally antagonistic when given together even though the response rate altering effects of each agent were in the same direction. These findings establish an additional behavioral effect of exogenously administered TRH in primates and suggest that barbiturates might alter behavior in part through an interaction with brain TRH receptive mechanisms.

Animals↗
PubMed1979

A comparison of clozapine, chlorpromazine, and thioridazine upon DRL performance in the squirrel monkey.

Clozapine (0.16--10 mg/kg, p. o.), chlorpromazine (0.25--2 mg/kg, p. o.), and thioridazine (0.25--2 mg/kg, p. o.) were administered to squirrel monkeys subjected to a DRL 10 s schedule. The reinforcer consisted of 50% unsweetened orange juice. Chlorpromazine and thioridazine had no effect at the lower doses, but decreased response rate at the highest dose. Clozapine increased response rates at the low doses (0.31--2.5 mg/kg) and decreased rates at the high dose (10 mg/kg). Clozapine appears to show a major difference from other neuroleptic drugs in this test by increasing response rate. Since clozapine produces few extrapyramidal side effects in man, this procedure may be useful in selecting and developing new anti-psychotic drugs with less liability for side effects.

Animals↗
PubMed1979

Cocaine, d-amphetamine, and pentobarbital effects on responding maintained by food or cocaine in rhesus monkeys.

The effects of IM injections of cocaine, d-amphetamine, and pentobarbital were studied in rhesus monkeys whose lever-press responding was maintained under a second-order fixed-interval, fixed ratio schedule of reinforcement. Within each session, fixed-interval components, ending with the IV injection of 30 microgram/kg cocaine (one group of monkeys) or the delivery of a 300 mg food pellet (second group of monkeys), alternated with fixed-interval components ending without an injection of cocaine or the delivery of food (extinction). Drug pretreatments generally caused comparable dose-related decreases in the overall rates of responding reinforced either by cocaine or by food. Response rates during extinction usually increased and then decreased as the dose of each drug increased. An analysis of the drug effects on response rates in different temporal segments of the fixed intervals showed that in both the reinforcement and extinction components, the normally low control rates of responding which occurred earlier in the intervals were usually increased, while higher control rates which occurred later in the intervals were increased less or decreased. Thus, the effects of these drugs were relatively independent of the reinforcing event (food or cocaine) and tended to depend more on the ongoing rate of responding under these conditions.

Animals↗
PubMed1983

Effects of cocaine, chlordiazepoxide, and chlorpromazine on responding of squirrel monkeys under second-order schedules of IM cocaine injection or food presentation.

Lever pressing by squirrel monkeys was maintained under second-order schedules of either food presentation or IM cocaine injection. Under one second-order schedule, every tenth response produced a brief (1-s) visual stimulus and the first brief stimulus presented after 30 min had elapsed was followed either by ten 300 mg food pellets or by a 3.0 mg IM injection of cocaine. Under another second-order schedule, the first response after 3 min produced the brief stimulus and the tenth brief stimulus was followed either by food or by cocaine. The two types of second-order schedules generated distinctly different patterns of responding. Furthermore, the temporal distribution of responding maintained by food presentation or cocaine injection sometimes differed slightly under the same schedule. Food presentation or cocaine injection occurred only at the end of each daily session, thereby allowing assessment of the effects of presession administration of cocaine, chlorpromazine (CPZ), and chlordiazepoxide (CDP) on responding at times when the direct effects of consequent cocaine injections were minimal or absent. Presession treatment with suitable doses of cocaine increased low rates of food- or cocaine-maintained responding under both types of second-order schedules, whereas CPZ only decreased responding. CDP increased responding in some monkeys, whereas in other monkeys it had little or no effect. Individual differences in the effects of CDP were not related to the schedule of reinforcement, the maintaining event, or the control rate of responding. Thus, the behavioral effects of cocaine, CDP, and CPZ were largely independent of whether responding was maintained by food or by cocaine.

Animals↗
PubMed1975

Influence of delta9-tetrahydrocannabinol on partial reinforcement effects.

Two experiments were performed with rats trained with either continuous reinforcement (food) or random 50% partial reinforcement for running in a straight alley. Half the rat were trained with daily injections of 0.5 mg/kg delta9-tetrahydrocannabinol (THC) and half with vehicle injections, all animals being extinguished with vehicle injections in Expt. 1 and with THC injections in Expt. 2. The partial reinforcement acquistion effect was abolished by THC during training; the partial reinforcement extinction effect was abolished by THC either during training of during extinction. In these respects THC resembles amylobarbitone and alcohol.

Animals↗
PubMed1982

Stimulant actions of histamine H1 antagonists on operant behavior in the squirrel monkey.

Squirrel monkeys were studied under fixed-interval schedules of reinforcement in which the first response (lever press) after a fixed period time resulted either in the delivery of a food pellet or in the termination of stimuli associated with impending electric shock delivery. Benztropine mesylate (0.03-1.7 mg/kg), promethazine HCl (0.3-10 mg/kg), and diphenhydramine HCl (0.3-17 mg/kg) all produced marked increases in responding at intermediate doses. The increases in responding were at least as great as those observed with psychomotor stimulants, such as amphetamine, in this species under similar behavioral conditions. Benztropine was most potent and diphenhydramine was least potent in most monkeys and, in some, promethazine and diphenhydramine were about equipotent. The order of potency and the magnitude of potency differences among the drugs suggest that the behavioral effects were due to antagonist actions at histamine H1 receptors, rather than to effects on dopamine uptake or on muscarinic receptors.

Animals↗
PubMed1982

Generalization of the discriminative stimulus properties of phencyclidine to other drugs in the pigeon using color tracking under second order schedules.

Pigeons were trained to track the location of a red or green key color under a second order schedule, with reinforcement of responses to each color contingent upon whether 1.5 mg/kg phencyclidine (PCP) or saline had been administered before the session. When cumulative dose-effect curves were determined for other drugs substituted for PCP, pigeons responded predominantly on the PCP key after other doses of PCP, ketamine, pentobarbital, d-cyclazocine and l-cyclazocine, but not after saline, lactic acid solution, d-amphetamine, chlordiazepoxide, scopolamine, morphine, naltrexone, or d-, or l-methadone. l-Cyclazocine was slightly more potent than d-cyclazocine in producing PCP key responding. PCP key responding after the optical isomers of cyclazocine was not blocked by naltrexone.

Animals↗
PubMed1980

Intravenous self-administration of cocaine and norcocaine by dogs.

The potency of cocaine, relative to d-amphetamine, to initiate and maintain intravenous self-administration behavior by dogs (n = 5) was determined. Response-contingent infusions of cocaine (at unit doses of 0.15, 0.30 and 0.60 mg/kg/infusion) and d-amphetamine (at unit doses of 0.05 and 0.10 mg/kg/infusion) were available during daily 4-h sessions on a FR1 reinforcement schedule. By comparing the dose-response curves of the two drugs, it was found that 1 mg of amphetamine is equivalent to 5.3 mg of cocaine (95% confidence limits = 3.8--9.1 mg). In a second experiment, pretreatment with the alpha-adrenergic antagonist phenoxybenzamine (in doses ranging from 0.125--2.0 mg/kg, IV) did not produce any appreciable changes in responding for cocaine (0.2 mg/kg/infusion) by dogs (n = 9). In contrast, when the same animals were pretreated with the dopaminergic antagonist pimozide (in doses ranging from 5--40 mg/kg, IV), subsequent responding for cocaine was increased in a dose-dependent manner. In a third experiment it was determined that norcocaine, the N-demethylated metabolite of cocaine, would maintain self-administration behavior by dogs (n = 4) when it was substituted for cocaine. As expected, when saline was substituted for cocaine, responding was not maintained.

Animals↗
PubMed1989

Nucleus accumbens as a substrate for the aversive stimulus effects of opiate withdrawal.

Previous studies from our laboratory using methylnaloxonium, a hydrophilic antagonist, showed that opiate receptors in the region of the nucleus accumbens are important for the acute reinforcing effects of heroin in non-dependent rats. A similar increased sensitivity to the response disruptive effects of intracerebrally injected methylnaloxonium in opiate dependent rats was observed in a fixed-ratio (FR) baseline of operant behaviors. These results suggest that the same opiate receptors in the region of the nucleus accumbens important for the positive reinforcing stimulus properties of opiates may also be responsible for the response disruptive, aversive stimulus properties of opiate withdrawal. These results also suggest that the neural substrates of some aspects of dependence may be partly related to those of the reinforcing effects of opiates. In particular, it is hypothesized that "euphoria" and "dysphoria" induced by opiates may reflect opponent motivational processes operating at a cellular level within the nucleus accumbens.

Animals↗
PubMed1989

Effects of fixed ratio size and dose on phencyclidine self-administration by rats.

Female Sprague-Dawley rats were trained to self-administer phencyclidine (PCP; 0.125, 0.25, or 0.5 mg/kg/injection) on a fixed ratio (FR) schedule of reinforcement under limited access conditions (3 h). Initial training began with cocaine, which was later replaced with ketamine and then one of the three unit doses of PCP. Baseline rates of injection were determined at FR 10. The size of the ratio was then incremented geometrically every fifth daily session. Increasing the ratio resulted in a decrease in the number of injections per session. Furthermore, this decrease was greater for the 0.25 mg/kg dose than for the 0.5 mg/kg unit dose. The self-administration of the 0.125 mg/kg dose was variable and rapidly extinguished upon the increase in fixed ratio. The results indicate that PCP is self-administered by rats under the conditions imposed in this study. Furthermore, the relative reinforcing efficacy of the different unit doses of PCP could be discriminated using this type of response cost procedure.

Animals↗